The present invention relates to group A streptogramin derivatives of formula (I): 
which have advantageous antibacterial activity.
Among the known streptogramins, pristinamycin (RP 7293), an antibacterial agent of natural origin produced by Streptomyces pristinaespiralis, was isolated for the first time in 1955. The pristinamycin sold under the name Pyostacine(copyright) comprises mainly pristinamycin IIA combined with pristinamycin IA.
Another antibacterial agent of the streptogramin class, virginiamycin, was isolated from Streptomyces virginiae, ATCC 13161 [Antibiotics and Chemotherapy, 5, 632 (1955)]. Virginiamycin (Staphylomycine(copyright)) comprises mainly factor M1 (VM1) combined with factor S (VS).
F. Le Goffic et. al., Transformations of Pristinamycin II to Study Its Mechanism of Action, 16(1) Eur. J. Medicinal Chemistry 69 (January-February 1981), have disclosed the preparation of dihydroxy derivatives of pristinamycin IIA.
Great Britain patent application GB-A-2 206 879 discloses modified group A streptogramin derivatives of structure: 
wherein:
R is a substituted alkyl radical or a heterocyclic radical and
n is 1 or 2, however, these derivatives show no activity orally.
The inventors have now found that the group A streptogramin derivatives of formula (I): 
wherein:
R1 is chosen from alkyl groups, alkenyl groups, alkynyl groups which may be mono- or polyfluoro groups, C3-C6 cycloalkyl groups, a phenylmethyl group, and heterocyclylmethyl groups, wherein said heterocyclyl portion is aromatic,
R2 is chosen from a hydrogen atom, a methyl group, and an ethyl group,
the bond  is a single bond (27R stereochemistry) or a double bond,
unless otherwise stated, the alkyl groups are chosen from straight and branched C1-C6 alkyl groups,
unless otherwise stated, the alkenyl groups are chosen from straight and branched C3-C6 alkenyl groups, and
unless otherwise stated, the alkynyl groups are chosen from straight and branched C3-C6 alkynyl groups, have advantageous antibacterial activity, alone or when combined with at least one group B streptogramin derivative.
In one embodiment of the invention, for example, when R1 is a heterocyclylmethyl group, the heterocyclyl portion can, for example, be chosen from a pyrrolyl group, a furyl group, a thienyl group, an imidazolyl group, and a pyridyl group.
In one embodiment of the invention, for example, when R1 is chosen from alkyl groups mono- or polysubstituted with a fluorine atom, the alkyl groups can, for example, be chosen from C1 and C2 alkyl groups.
In another embodiment, for example, R1 can be chosen from alkenyl groups, such as, an allyl group. In yet another embodiment, R1 can be chosen from alkynyl groups, such as, for example, a propargyl group.
The streptogramin derivatives of formula (I) may be prepared, for example, by:
(a) reacting, in the presence of a phase-transfer agent, a derivative of formula (IIa):
R1xe2x80x94Xxe2x80x83xe2x80x83(IIa) 
xe2x80x83wherein:
R1 is chosen from alkyl groups, alkenyl groups, alkynyl groups which may be mono- or polyfluoro groups, C3-C6 cycloalkyl groups, a phenylmethyl group, and heterocyclylmethyl groups, wherein said heterocyclyl portion is aromatic, and
X is chosen from halogen atoms, a methylsulphonyloxy group, a p-toluenesulphonyloxy group, and a trifluoromethylsulphonyloxy group, with a dihydroxy streptogramin derivative of formula (II): 
xe2x80x83wherein:
R2 is chosen from a hydrogen atom, a methyl group, and an ethyl group,
the bond  is a single bond (27R stereochemistry) or a double bond, and
(b) optionally protecting with a protecting group, prior to said reacting, the hydroxyl function in position 14, and then, where appropriate, removing said protecting group from position 14, and
(c) optionally protecting with a protecting group, prior to said reacting, the amide function in position 8, and then, where appropriate, removing said protecting group from position 8.
In one embodiment of the invention, for example, when X is chosen from halogen atoms, a derivative of formula (IIa), wherein X is chosen from a bromine atom and an iodine atom, can be used for said reacting.
The phase-transfer agent can, for example, be chosen from quaternary ammonium derivatives, for example, salts of tetraalkylammonium and salts of trialkylbenzylammonium, such as, chloride, bromide, and sulphate salts.
Said reacting can, for example, be carried out in a basic medium, such as, for example, a basic medium comprising at least one agent chosen from sodium hydroxide, potassium hydroxide, potassium carbonate, and caesium carbonate.
Said reacting can also, for example, be carried out in an aqueous-organic medium, such as, for example, an aqueous-organic medium comprising at least one agent chosen from hydrocarbons (for example, toluene), halogenated solvents (for example, dichloromethane), and esters (for example, ethyl acetate).
Said reacting can, for example, take place at a temperature ranging, for example, from 10xc2x0 C. to 60xc2x0 C., such as, for example, at about 20xc2x0 C.
The process, for example, can also be performed in the presence of an excess of the derivative of formula (IIa).
The protection and deprotection of the hydroxyl radical in position 14 and of the amide radical in position 8 can be carried out according to known, art-recognized methods which do not affect the rest of the molecule, such as, for example, by applying the methods described by T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis (2nd edition), A. Wileyxe2x80x94Interscience Publication (1991) or by Mc Omie, Protective Groups in Organic Chemistry, Plenum Press (1973). For example, the protection of the hydroxyl radical in position 14 can be carried out with an allyl protecting group which can be installed and removed by analogy with the methods described below in the examples. The protection of the amide in position 8 may, for example, be carried out with a t-butoxycarbonyl protecting group.
When the reaction leads to a mixture of the 14- and 16-O-alkyl isomers, these isomers may be separated according to known, art-recognized methods which do not affect the rest of the molecule, such as, for example, by chromatography, i.e., high performance liquid chromatography (HPLC) on a normal or reverse phase, on a chiral or non-chiral phase, or by flash chromatography, by crystallization, or by any other appropriate separation technique known in the art.
According to the invention, the streptogramin derivatives of formula (I) may also be prepared, for example, by a process comprising:
(a) desilylation of a silyl and 14-O-allyl derivative of formula (III): 
xe2x80x83wherein:
R2 is chosen from a hydrogen atom, a methyl group, and an ethyl group,
the bond  is a single bond (27R stereochemistry) or a double bond,
R3 is a protecting group, and
R4 is a silyl group,
(b) 37-O-alkylation of the product obtained in (a) above, and
(c) removal of the 14-O-allyl group and the R3 protecting group according to known methods which do not affect the rest of the molecule.
In one embodiment of the invention, the protecting group R3 can, for example, be a t-butoxycarbonyl group.
Representative R4 silyl groups include, for example, trialkylsilyl groups, dialkylphenylsilyl groups, and alkyldiphenylsilyl groups, for example, a t-butyldiphenylsilyl group and a t-butyldimethylsilyl group.
The desilylation, for example, can be carried out according to known, art-recognized methods which do not affect the rest of the molecule. The process can, for example, be performed in the presence of a source of fluoride ions, such as, for example, tetra-n-butylammonium fluoride or, for example, a hydrofluoric acid/amine complex, wherein the amine, for example, can be an amine chosen from triethylamine and pyridine. The reaction, for example, can be carried out in a chlorinated solvent (for example, dichloromethane) or in an ether (for example, tetrahydrofuran) at a temperature ranging, for example, from 20xc2x0 C. to 80xc2x0 C.
The 37-O-alkylation reaction, for example, can be carried out by reacting a derivative of formula (IIa) as defined above, with the desilylated streptogramin of formula (III). This process can be performed under an inert atmosphere (for example, under nitrogen or argon), in basic medium, for example, in the presence of sodium hydride, alkali metal (for example, lithium, sodium, or potassium) hexamethyldisilylamide, or in the presence of an organolithium reagent (for example, n-butyllithium), or alternatively in the presence of an amide (for example, lithium diisopropylamide), in an inert solvent such as an amide (for example, dimethylformamide) or an ether (for example, tetrahydrofuran), at a temperature ranging, for example, from xe2x88x9220xc2x0 C. to 60xc2x0 C.
Removal of the allyl group can be carried out, for example, in the presence of a proton donor such as 4-methylphenylsulphinic acid, in the presence of a palladium catalyst, for example, tetrakis(triphenylphosphine)-palladium, in a chlorinated solvent, for example, dichloromethane, at a temperature ranging, for example, from 0xc2x0 C. to 60xc2x0 C. It is also possible to perform the process according to the methods described in the references cited above. The t-butoxycarbonyl group can, for example, be removed according to known methods which do not affect the rest of the molecule, such as, for example, in a solvent such as dimethyl sulphoxide, dimethylforrnamide or diphenyl ether, at a temperature ranging, for example, from 130xc2x0 C. to 170xc2x0 C.
The streptogramin derivative of formula (III) may be prepared, for example, by 36-O-allylation and then 37-O-silylation and protection of the amide in position 8 with a radical R3, and where appropriate optionally removing the protecting group R3.
The 36-O-allylation can be carried out according to known, art-recognized methods, such as, for example, those cited in the above references. For example, the 36-O-allylation may be carried out by reacting an allyl halide (for example, bromide) or a methylsulphonyloxy derivative, p-toluenesulphonyloxy derivative, or a trifluoromethylsulphonyloxy derivative in the presence of a base, such as a carbonate (for example, potassium carbonate or caesium carbonate), in a solvent, such as a ketone (for example, methyl ethyl ketone), a nitrile (for example, acetonitrile) or a hydrocarbon (for example, toluene), at a temperature ranging, for example, from 40xc2x0 C. to 80xc2x0 C., such as, for example, about 70xc2x0 C.
The silylation may be carried out, for example, according to known, art-recognized methods which do not affect the rest of the molecule, such as by using a halide (for example, a chloride) of the silyl group R4. For example, the process can be performed using trialkylsilyl chloride, dialkylphenylsilyl chloride or alkyldiphenylsilyl chloride (for example, t-butyldiphenylsilyl chloride or t-butyldimethylsilyl chloride), working in a solvent, such as a chlorinated solvent (for example, dichloromethane), an amide (for example, dimethylformamide), an ether (for example, tetrahydrofuran), or a nitrile (for example, acetonitrile), at a temperature ranging, for example, from 0xc2x0 C. to 60xc2x0 C., such as, for example, at about room temperature.
The installation of the protecting group R3 can be carried out, for example, according to the methods mentioned above. For example, it can be carried out in the presence of an excess of di-t-butyl dicarbonate, a base (triethylamine or pyridine) and optionally a catalyst, such as 4-dimethylaminopyridine, in a chlorinated solvent (dichloromethane) or an ether (tetrahydrofuran) at a temperature ranging, for example, from 0xc2x0 C. to 80xc2x0 C.
For example, the dihydroxylated group A streptogramin derivative of formula (II) may be obtained by:
(a) selective reduction of a natural pristinamycin component of formula (IV): 
xe2x80x83wherein:
R2 is chosen from a hydrogen atom, a methyl group, and an ethyl group, and
the bond  is a single bond (27R stereochemistry) or a double bond, and
(b) separation of the 16S epimer form.
The reduction can be carried out, for example, in the presence of a reducing agent, such as an alkali metal borohydride, for example, sodium borohydride or sodium triacetoxyborohydride, in an organic solvent chosen from chlorinated solvents (for example, dichloromethane, dichloroethane or chloroform), tetrahydrofuran, acetic acid and alcohols such as methanol, ethanol or 2-propanol, at a temperature ranging, for example, from xe2x88x9278xc2x0 C. to 40xc2x0 C.
The separation of the 16R epimer form and of the 16S epimer form can be carried out, for example, according to known, art-recognized methods. For example, the separation of the epimer forms may be carried out by chromatography, flash chromatography, high performance liquid chromatography (HPLC), on a chiral or non-chiral phase, or centrifugal partition chromatography (CPC), starting with the mixture of the 16R and 16S epimers. Further, the separation may be carried out by crystallization, or by any other appropriate separation technique available in the art.
The pristinamycin derivatives of formula (IV) correspond, respectively, to pristinamycin IIA (PIIA), pristinamycin IIB (PIIB), pristinamycin IIC (PIIC), pristinamycin IID (PIID), pristinamycin IIF (PIIF), and pristinamycin IIG (PIIG), which are known components of natural pristinamycin. The components PIIF and PIIG have been disclosed in European patent application no. EP-A-0 614 910. Pristinamycin IIC (PIIC) and pristinamycin IID (PIID) may be obtained as described by J. C. Barrixc3xa8re et al., Expert. Opin. Invest. Drugs, 3(2), 115-31 (1994).
The present invention also relates to pristinamycin derivatives of formula (III), which are novel products.
The preparation and separation of the natural group A streptogramin components [streptogramins of formula (IV)] can be carried out, for example, by fermentation and isolation of the constituents from the fermentation must according to or by analogy with the method described by J. Preud""homme et al., Bull. Soc. Chim. Fr., vol. 2, 585 (1968), or in European patent application no. EP-A-0 614 910. Additionally, the preparation of natural group A components may be carried out, for example, by specific fermentation, as disclosed in French patent application no. FR-A-2 689 518.
The streptogramin derivatives of formula (I) may be purified, where appropriate, by physical methods such as crystallization, chromatography and Centrifugal Partition Chromatography (CPC).
The streptogramin derivatives according to the present invention have superior antibacterial properties and synergistic properties with respect to the antibacterial activity of the group B streptogramin derivatives. They are notably advantageous on account of their powerful activity, alone or in combination.
When at least one group A streptogramin derivative of the invention is combined with at least one group B streptogramin component or derivative, this component or derivative may be chosen, depending on whether it is desired to obtain a form for oral or parenteral administration, from natural group B streptogramin components, such as, for example, pristinamycin IA, pristinamycin IB, pristinamycin IC, pristinamycin ID, pristinamycin IE, pristinamycin IF, pristinamycin IG, virginiamycin S1, S3 or S4, vernamycin B or C, etamycin, and from semisynthetic derivatives as disclosed in U.S. Pat. Nos. or European patent application nos. U.S. Pat. Nos. 4,618,599, 4,798,827, 5,326,782, EP-A-0 772 630 and EP-A-0 770 132.
Representative group B streptogramin components and derivatives may include, for example, (I) streptogramin derivatives of formula (A), and salts thereof: 
wherein:
(1) Rb, Rc, Re, and Rf are each a hydrogen atom;
Rd is chosen from a hydrogen atom and a dimethylamino group; and
Ra is chosen from:
(A) xe2x80x94CH2Rxe2x80x2a groups, wherein Rxe2x80x2a is chosen from:
(i) a pyrrolidinyl-3-thio group,
(ii) a piperidyl-3-thio group,
(iii) a piperidyl-4-thio group,
wherein said groups (i)-(iii) may be unsubstituted or substituted with at least one group chosen from alkyl groups, and
(iv) alkylthio groups which are substituted with 1 or 2 groups chosen from:
(a) a hydroxysulfonyl group,
(b) alkylamino groups,
(c) dialkylamino groups, which may be unsubstituted or substituted with at least one group chosen from a mercapto group or dialkylamino groups,
(d) a piperazine ring which may be substituted or unsubstituted, a morpholino group, a thiomorpholino group, a piperidino group, a 1-pyrrolidinyl group, a 2-piperidyl group, a 3-piperidyl group, a 4-piperidyl group, a 2-pyrrolidinyl group, and a 3-pyrrolidinyl group, each of which may be unsubstituted or substituted with alkyl, and
(B) xe2x95x90CHRxe2x80x2a groups, wherein Rxe2x80x2a is chosen from:
(i) a pyrrolidinyl-3-amino group,
(ii) a piperidyl-3-amino group and a piperidyl-4--amino group,
(iii) a pyrrolidinyl-3-oxy group,
(iv) a piperidyl-3-oxy group and a piperidyl-4-oxy group,
(v) a pyrrolidinyl-3-thio group,
(vi) a piperidyl-3-thio group and a piperidyl-4-thio group,
wherein said groups (i)-(vi) may be unsubstituted or substituted with at least one group chosen from alkyl groups,
(vii) alkylamino groups,
(viii) alkyloxy groups, and
(ix) alkylthio groups,
wherein said groups (vii), (viii), and (ix) are substituted with 1 or 2 groups chosen from:
(a) a hydroxysulfonyl group,
(b) alkylamino groups,
(c) dialkylamino groups unsubstituted or substituted with at least one group chosen from dialkylamino groups,
(d) trialkylammonio groups,
(e) a 4-imidazolyl group, and a 5-imidazolyl group, each of which may be unsubstituted or substituted with alkyl,
(f) a piperazine ring which may be substituted or unsubstituted, a morpholino group, a thiomorpholino group, a piperidino group, a 1-pyrrolidinyl group, a 2-piperidyl group, a 3-piperidyl group, a 4-piperidyl group, a 2-pyrrolidinyl group, and a 3-pyrrolidinyl group, each of which may be unsubstituted or substituted with alkyl,
(C) a quinuclidinyl-3-thiomethyl group, and
(D) a quinuclidinyl-4-thiomethyl group; or
(2) Ra is a hydrogen atom, and
(a) Rb, Re, and Rf are each a hydrogen atom, and
Rd is chosen from a xe2x80x94NHCH3 group and a xe2x80x94N(CH3)2 group, and Rc is chosen from a chlorine atom and a bromine atom, or, when Rd is a xe2x80x94N(CH3)2 group, Rc is chosen from (C3-C5) alkenyl groups, or
(b) Rb, Rd, Re, and Rf are each a hydrogen atom, and
Rc is chosen from halogen atoms, aminomonoalkyl groups, aminodialkyl groups, alkyloxy groups, a trifluoromethyloxy group, thioalkyl groups, (C1-C3) alkyl groups, and trihalomethyl groups, or
(c) Rb, Rc, Re, and Rf are each a hydrogen atom, and
Rd is chosen from halogen atoms, an ethylamino group, a diethylamino group, a methylethylamino group, alkyloxy groups, a trifluoromethyloxy group, thioalkyl groups, (C1-C6) alkyl groups, aryl groups, and trihalomethyl groups, or
(d) Rb, Re, and Rf are each a hydrogen atom,
Rc is chosen from halogen atoms, aminomonoalkyl groups, aminodialkyl groups, alkyloxy groups, a trifluoromethyloxy group, thioalkyl groups, and (C1-C3) alkyl groups, and
Rd is chosen from halogen atoms, an amino group, aminomonoalkyl groups, aminodialkyl groups, alkyloxy groups, a trifluoromethyloxy group, thioalkyl groups, C1-C6) alkyl groups, and trihalomethyl groups, or
(e) Rc, Re, and Rf are each a hydrogen atom, and
Rb and Rd are each a methyl group,
and further, for example, (11) semisynthetic group B streptogramin derivatives of formula (B), and salts thereof: 
wherein:
(A) Y is chosen from (i) a nitrogen atom and (ii) xe2x95x90CR3xe2x80x94 groups, and
(1) when Y is chosen from xe2x95x90CR3xe2x80x94 groups, R1 is chosen from
(a1) a hydrogen atom, C1-C8 alkyl groups, and C2-C8 alkenyl groups,
(b1) C3-C8 cycloalkyl groups, and saturated and unsaturated 3- to 8-membered heterocyclyl groups,
(c1) an unsubstituted phenyl group,
(d1) a phenyl group substituted with at least one substituent chosen from halogen atoms, a hydroxyl group, alkyl groups, alkyloxy groups, alkylthio groups, alkylsulphinyl groups, alkylsulphonyl groups, an amino group, alkylamino groups, and dialkylamino groups, and
(e1) groups xe2x80x94NRxe2x80x2Rxe2x80x3, wherein:
Rxe2x80x2 and Rxe2x80x3, which are identical or different, are each chosen from a hydrogen atom, and C1-C3 alkyl groups, or
Rxe2x80x2 and Rxe2x80x3, form, together with the nitrogen atom to which they are attached, a 3- to 8-membered heterocyclyl group, wherein one of said members, in addition to said nitrogen atom, may be a hetercatom chosen from an oxygen atom, a sulphur atom, and a nitrogen atom, and wherein said heterocyclyl group is unsubstituted or substituted with a group chosen from alkyl groups, C2-C8 alkenyl groups, C3-C6 cycloalkyl groups, saturated and unsaturated 4- to 6-membered heterocyclyl groups, a benzyl group, an unsubstituted phenyl group, and a substituted phenyl group, as defined above in (d1),
(f1) halomethyl groups, a hydroxymethyl group, and alkyloxymethyl groups,
(g1) alkylthiomethyl groups, wherein said alkyl portion is unsubstituted or substituted with an xe2x80x94NRxe2x80x2Rxe2x80x3 group, and wherein said Rxe2x80x2 and said Rxe2x80x3 are as defined above in (e1),
(h1) alkylsulphinylmethyl groups, alkylsulphonylmethyl groups, an acyloxymethyl group, a benzoyloxymethyl group, a cyclopropylaminomethyl group, and xe2x80x94(CH2)nNRxe2x80x2Rxe2x80x3 groups, wherein n is chosen from integers ranging from 1 to 4, and wherein said Rxe2x80x2 and said Rxe2x80x3 are as defined above in (e1), and
(i1) when R3 is a hydrogen atom, R1 is additionally chosen from a formyl group, a carboxyl group, alkyloxycarbonyl groups, and xe2x80x94CONRxe2x80x2Rxe2x80x3 groups, wherein said Rxe2x80x2 and said Rxe2x80x3 are defined as above in (e1), and
(2) when Y is a nitrogen atom, R1 is chosen from
(a2) options (a1), (b1), (c1), (d1), and (e1) as defined above, and
(b2) XRo groups, wherein X is chosen from an oxygen atom, a sulphur atom, a sulphinyl group, a sulphonyl group, and an xe2x80x94NHxe2x80x94 group, and wherein Ro is chosen from (i) (C1 to C8) alkyl groups, (ii) (C3 to C6) cycloalkyl groups, (iii) saturated and unsaturated 3- to 8-membered heterocyclyl groups, (iv) 3- to 8-membered heterocyclylmethyl groups in which the heterocyclyl portion is attached to the methyl group by a carbon atom, (v) an unsubstituted phenyl group, (vi) phenyl groups substituted with at least one group chosen from halogen atoms, a hydroxyl group, alkyl groups, alkyloxy groups, alkylthio groups, alkylsulfinyl groups, alkylsulfonyl groups, an amino group, alkylamino groups, and dialkylamino groups, (vii) xe2x80x94(CH2)nNRxe2x80x2Rxe2x80x3 groups, wherein Rxe2x80x2 and Rxe2x80x3 are as defined above in (e1), and wherein n is chosen from integers ranging from 2 to 4, and (viii) if X is an NH group, Ro may also be a hydrogen atom;
(B) R2 is chosen from a hydrogen atom and C1-C3 alkyl groups,
(C) R3 is chosen from a hydrogen atom, alkyl groups, a carboxyl group, alkyloxycarbonyl groups, and carbamoyl groups of formula xe2x80x94COxe2x80x94NRxe2x80x2Rxe2x80x3, wherein said Rxe2x80x2 and said Rxe2x80x3 are defined as above in (e1),
(D) Ra is chosen from a methyl group and an ethyl group, and
(E) Rb, Rc, and Rd are defined as follows:
(1) Rb and Rc are each a hydrogen atom and
Rd is chosen from a hydrogen atom, a methylamino group, and a dimethylamino group, or
(2) Rb is a hydrogen atom,
Rc is chosen from a hydrogen atom, a chlorine atom, a bromine atom, and C3-C5 alkenyl groups, and
Rd is chosen from xe2x80x94N(CH3)Rxe2x80x2xe2x80x3 groups, wherein
Rxe2x80x2xe2x80x3 is chosen from
(a) alkyl groups,
(b) C2-C4 hydroxyalkyl groups,
(c) C2-C8 alkenyl groups, wherein said C2-C8 alkenyl groups are unsubstituted or substituted with (i) an unsubstituted phenyl group, (ii) a cycloalkyl(C3-C6)methyl group, (iii) an unsubstituted benzyl group, (iv) a benzyl group substituted with at least one substituent chosen from halogen atoms, a hydroxyl group, alkyl groups, alkyloxy groups, alkylthio groups, alkylsulphinyl groups, alkylsuliphonyl groups, an amino group, alkylamino groups, and dialkylamino groups, or (v) heterocyclylmethyl groups and heterocyclylethyl groups, wherein said heterocyclyl portions of said heterocyclylmethyl groups and said heterocyclylethyl groups are chosen from saturated and unsaturated 5- to 6-membered heterocyclyl groups comprising from 1 to 2 heteroatoms chosen from a sulphur atom, an oxygen atom, and a nitrogen atom, and wherein said heterocyclyl groups may be unsubstituted or substituted with a group chosen from alkyl groups, C2-C8 alkenyl groups, C3-C6 cycloalkyl groups, saturated and unsaturated 4- to 6-membered heterocyclyl groups, an unsubstituted phenyl group, a benzyl group, or a substituted phenyl group as defined above in (d1),
(d) a cyanomethyl group,
(e) xe2x80x94CH2CORe groups, wherein Re is chosen from (i) xe2x80x94ORxe2x80x2e groups, wherein Rxe2x80x2e is chosen from a hydrogen atom, C1-C6 alkyl groups, C2-C6 alkenyl groups, a benzyl group, and heterocyclylmethyl groups, wherein said heterocyclyl portion is chosen from 5- to 6-membered heterocyclyl groups comprising from 1 to 2 heteroatoms chosen from a sulphur atom, an oxygen atom, and a nitrogen atom, (ii) alkylamino groups, alkylmethylamino groups, heterocyclylamino groups and heterocyclylmethylamino groups, wherein said heterocyclyl portion of said heterocyclylamino groups and said heterocyclylmethylamino groups is chosen from 5- to 6-membered saturated heterocyclyl groups comprising from 1 to 2 heteroatoms chosen from a sulphur atom, an oxygen atom, and a nitrogen atom, and wherein said heterocyclyl groups may be unsubstituted or substituted with a group chosen from alkyl groups, a benzyl group, and alkyloxycarbonyl groups, or
(3) Rb is a hydrogen atom,
Rd is chosen from an xe2x80x94NHCH3 group and an xe2x80x94N(CH3)2 group, and
Rc is chosen from a chlorine atom, and a bromine atom, and when Rd is an xe2x80x94N(CH3)2 group, Rc is chosen from C3-C5 alkenyl groups, or
(4) Rb and Rd are each a hydrogen atom, and
Rc is chosen from halogen atoms, alkylamino groups, dialkylamino groups, alkyloxy groups, a trifluoromethoxy group, thioalkyl groups, C1-C6 alkyl groups, and trihalomethyl groups, or
(5) Rb and Rc are each a hydrogen atom, and
Rd is chosen from halogen atoms, an ethylamino group, a diethylamino group, a methylethylamino group, alkyloxy groups, a trifluoromethoxy group, alkylthio groups, alkylsulphinyl groups, alkylsulphonyl groups, C1-C6 alkyl groups, a phenyl group, and trihalomethyl groups, or
(6) Rb is a hydrogen atom, and
Rc is chosen from halogen atoms, alkylamino groups, dialkylamino groups, alkyloxy groups, a trifluoromethoxy group, thioalkyl groups, and C1-C3 alkyl groups, and
Rd is chosen from halogen atoms, an amino group, alkylamino groups, dialkylamino groups, alkyloxy groups, a trifluoromethoxy group, thioalkyl groups, C1-C6 alkyl groups, and trihalomethyl groups, or
(7) Rc is a hydrogen atom, and
Rb and Rd are each a methyl group, and
even further, for example, (III) semisynthetic group B derivatives of formula (C), and salts thereof, when salts exists: 
wherein:
(A) R is chosen from
(1) xe2x80x94NR1R2 groups, wherein R1 and R2, which may be identical or different, are each chosen from
(i) a hydrogen atom,
(ii) (C1-C8) alkyl groups,
(iii) (C1-C8) alkyl groups substituted with a hydroxyl group,
(iv) (C3-C8) alkenyl groups,
(v) (C3-C8) cycloalkyl groups,
(vi) (C1-C8) alkyloxy groups,
(vii) dialkylamino groups,
(viii) phenylalkyl groups,
(ix) phenylalkyl groups substituted with at least one group chosen from halogen atoms, alkyl groups, hydroxyalkyl groups, alkyloxy groups, and dialkylamino groups, and
(x) 3- to 8-membered saturated and unsaturated heterocyclylalkyl groups comprising at least one hetero atom chosen from nitrogen, oxygen, and sulphur, or
(xi) R1 and R2 form, together with the nitrogen atom to which they are attached, a saturated, partially saturated or unsaturated mono- or polycyclic 3- to 12-membered heterocycle group, wherein one of said members, in addition to said nitrogen atom, may be an atom chosen from oxygen, sulphur, and nitrogen, and wherein said heterocyclyl group is unsubstituted or substituted with at least one group chosen from a hydroxyl group, alkyl groups, an unsubstituted phenyl group, a phenyl group substituted with a halogen atom, phenylalkyl groups, phenyl(C2-C4)alkenyl groups, hydroxyalkyl groups, acyl groups, alkyloxycarbonyl groups, heterocyclyl groups and heterocyclylcarbonyl groups, wherein the heterocyclyl portion is saturated or unsaturated (4-to 6-membered) and comprises at least one hetero atom chosen from nitrogen, sulphur, and oxygen, and
(2) xe2x80x94SR3 groups, wherein R3 is chosen from
(i) (C1-C8) alkyl groups and(C3-C8) cycloalkyl groups substituted with xe2x80x94NR1R2, wherein R1 and R2, which may be identical or different, are each chosen from a hydrogen atom and alkyl groups, or form, together with the nitrogen atom to which they are attached, a heterocycle as defined in (xi) above, and
(ii) saturated and unsaturated heterocyclyl and heterocyclylmethyl (3- to 7-membered) groups, wherein one of said members, in addition to said nitrogen atom, may be an atom chosen from oxygen, sulphur, and nitrogen, and wherein said heterocyclyl portion is unsubstituted or substituted with an alkyl group, 
xe2x80x83is a residue of an unsaturated ring which is not substituted in the 5xcex3 position 
or the residue of a saturated ring which is substituted in the 5xcex3 position with a fluorine atom 
(C) Ra is chosen from a methyl group and an ethyl group, and
(D) Rb, Rc and Rd are defined below:
1) Rb and Rc are each a hydrogen atom, and
Rd is chosen from a hydrogen atom, a methylamino group, and a dimethylamino group, or
2) Rb is a hydrogen atom,
Rc is chosen from a hydrogen atom, a chlorine atom, a bromine atom, and a (C3 to C5) alkenyl group, and
Rd is xe2x80x94N(CH3)xe2x80x94Rxe2x80x2xe2x80x3, wherein Rxe2x80x2xe2x80x3 is chosen from:
(1) alkyl groups, (2) (C2 to C4) hydroxyalkyl groups, (3) (C2 to C8) alkenyl groups, (4) phenylalkenyl groups, (5) cycloalkyl(C3 to C6)methyl groups, (6) an unsubstituted benzyl group, (7) a substituted benzyl group, (8) heterocyclylmethyl groups and heterocyclylethyl groups, (9) a xe2x80x94CH2CN group, (10) a xe2x80x94CH2COOH group, and (11) xe2x80x94CORe groups and xe2x80x94CH2CORe groups for which either:
(a) Re is xe2x80x94ORxe2x80x2e, wherein Rxe2x80x2e is chosen from a hydrogen atom, C1-C6 alkyl groups, C2-C6 alkenyl groups, a benzyl group, and heterocyclylmethyl groups, wherein said heterocyclyl portion is chosen from 5- to 6-membered heterocyclyl groups comprising from 1 to 2 heteroatoms chosen from a sulphur atom, an oxygen atom, and a nitrogen atom, or
(b) Re is chosen from alkylamino groups, alkylmethylamino groups, heterocyclylamino groups, and heterocyclylmethylamino groups, or
3) Rb is a hydrogen atom,
Rd is chosen from an xe2x80x94NHCH3 group and an xe2x80x94N(CH3)2 group, and
Rc is chosen from a chlorine atom, and a bromine atom, and when Rd is an xe2x80x94N(CH3)2 group, Rc is chosen from C3-C5 alkenyl groups, or
4) Rb and Rd are each a hydrogen atom, and
Rc is chosen from halogen atoms, alkylamino groups, dialkylamino groups, alkyloxy groups, a trifluoromethoxy group, thioalkyl groups, (C1-C6) alkyl groups, and trihalomethyl groups, or
5) Rb and Rc are each a hydrogen atom, and
Rd is chosen from halogen atoms, an ethylamino group, a diethylamino group, a methylethylamino group, alkyloxy groups, a trifluoromethoxy group, alkylthio groups, alkylsulphinyl groups, alkylsulphonyl groups, (C1-C6) alkyl groups, a phenyl group, and trihalomethyl groups, or
6) Rb is a hydrogen atom,
Rc is chosen from halogen atoms, alkylamino groups, dialkylamino groups, alkyloxy groups, a trifluoromethoxy group, thioalkyl groups, (C1-C3) alkyl groups, and
Rd is chosen from halogen atoms, an amino group, alkylamino groups, dialkylamino groups, alkyloxy groups, a trifluoromethoxy group, thioalkyl groups, (C1-C6) alkyl groups, and trihalomethyl groups, or
7) Rc is a hydrogen atom, and
Rb and Rd are each a methyl group.
It is understood that the combinations formed from the derivatives according to the invention and from group B streptogramins also fall within the context of the present invention.
The group B streptogramin derivatives of formula (B) may be prepared, for example, according to the methods disclosed in International patent application no. PCT/FR 99/00409. The group B streptogramin derivatives of formula (C) may be prepared, for example, according to the methods disclosed in International patent application no. PCT/FR 00/02146.
In vitro on Staphylococcus aureus IP8203, the streptogramin derivatives according to the invention have been shown to be active at concentrations ranging, for example, from 0.06 to 32 xcexcg/ml, alone or combined with at least one group B derivative such as pristinamycin IB. In vivo, the streptogramin derivatives according to the invention synergized the antimicrobial activity of pristinamycin IB on experimental infections of mice with Staphylococcus aureus IP8203 at doses; ranging, for example, from 32 to 150 mg/kg orally (DC50).
Representative streptogramin derivatives of formula (I) include, for example, streptogramin derivatives of formula (I) wherein:
R1 is chosen from alkyl groups, alkenyl groups, and alkynyl groups,
R2 is a methyl group, and
the bond  is a single bond (27R stereochemistry) or al double bond. The compounds described below in the Examples are exemplary of such products.
The compounds according to the invention are advantageous on account of their low toxicity. None of the compounds of the invention has shown any toxicity at doses of 150 mg/kg on Staphylococcus aureus IP8203, when administered twice a day subcutaneously or orally in mice.
Representative group A streptogramin derivatives of formula (I), which may be used according to the invention, for example, include the compounds mentioned below in the examples, and the following compounds:
(16R)-16-deoxo-16-trifluoromethoxypristinamycin IIB 
(16R)-16-deoxo-16-trifluoromethoxypristinamycin IIA 
(16R)-16-deoxo-16-difluoromethoxypristinamycin IIB 
(16R)-16-deoxo-16-difluoromethoxypristinamycin IIA 
(16R)-16-deoxo-16-fluoromethoxypristinamycin IIB 
(16R)-16-deoxo-16-fluoromethoxypristinamycin IIA 
(16R)-16-deoxo-16-cyclopropyloxypristinamycin IIB 
(16R)-16-deoxo-16-cyclopropyloxypristinamycin IIA 
(16R)-16-deoxo-16-cyclobutyloxypristinamycin IIB 
(16R)-16-deoxo-16-cyclobutyloxypristinamycin IIA 
(16R)-16-deoxo-16-isopropyloxypristinamycin IIB 
(16R)-16-deoxo-16-isopropyloxypristinamycin IIA 
(16R)-16-deoxo-16-(2-fluoropropen-3-yloxy)pristinamycin IIB 
(16R)-16-deoxo-16-(2-fluoropropen-3-yloxy)pristinamycin IIA.
The examples which follow, given without any implied limitation, illustrate the present invention.
In the examples which follow, the 16-deoxopristinamycin IIA (or IIB) nomenclature indicates the replacement of the ketone function in position 16 with 2 hydrogen atoms. As the chromatography proceeded, all the fractions were analyzed by thin layer chromatography (TLC) on Merck 60F254 silica plates. The fractions corresponding to the same spot on TLC were combined and then concentrated to dryness, under reduced pressure (30xc2x0 C.; 2.7 kPa). The residues thus obtained were analyzed by known, art-recognized spectroscopic techniques (NMR; IR; MS), allowing the expected product to be identified.